This grant will focus on the clinical evaluations of all members of families with two or more persons affected by pulmonary fibrosis to establish phenotypes, followed by the use of standard genetic methodology (linkage analysis) to investigate the distribution of polymorphic markers in relation to the phenotypic expression of pulmonary fibrosis. He will focus not only on the assessment of individual subjects, data analysis and publication of his results, but also on the maintenance of quality with regards to subject recruitment, protocol adherence and data management. Once completed, this preliminary study should provide strong rationale to pursue the identification of candidate genes on the basis of both positional and functional criteria and to perform a mutation analysis for strong candidate genes among patients with familial pulmonary fibrosis. This can then be followed up by an investigation into whether the genes that are found to play a role in familial pulmonary fibrosis are important in other more common forms of pulmonary fibrosis, such as idiopathic pulmonary fibrosis or asbestosis. Throughout Dr. Will's career development, he will interface with trainees in genetics, environmental health, and pulmonary medicine. This intellectually rich environment will help to foster the career development of Dr. Will, providing ample opportunity for critical review throughout the period of this award. Both the mentor and the institution are highly committed to Dr. Will's scientific development and academic success.